BETA-ARRESTINS REGULATE MITOGENIC SIGNALING AND CLATHRIN-MEDIATED ENDOCYTOSIS OF THE INSULIN-LIKE-GROWTH-FACTOR-I RECEPTOR

beta-Arrestins mediate agonist-dependent desensitization of G protein- coupled receptors and target the receptors to clathrin-coated pits for internalization. Here we report an expanded role of beta-arrestins in promoting clathrin-mediated endocytosis of a tyrosine kinase growth f actor receptor, ie. the insulin-like growth factor I (IGF-1) receptor. beta-Arrestins bind to the ligand-occupied IGF-1 receptors, promote t heir endocytosis, and enhance IGF-l-dependent mitogen-activated protei n kinase phosphorylation and DNA synthesis. Our results suggest a role for beta-arrestins in regulating mitogenic signaling and clathrin-med iated endocytosis of receptors not classically coupled to G proteins.